tbuckley/cabot-search huggingface dataset:
Reflex MammaPrint testing on breast core biopsies: A single center experience.
Authors: Colleen Kerrigan, Nicole Look Hong, Amanda Roberts, Sharon Nofech-Mozes, Tanya Jorden, Sonal Gandhi
Journal: Journal of Clinical Oncology (2023)

e12581 Background: Breast cancer genomic assays are well established in the adjuvant setting, but still evolving in the neoadjuvant setting. Recent data shows that MammaPrint (MP)/BluePrint (BP) genomic assays in the neoadjuvant setting can reclassify hormone receptor positive (HR+), HER2 negative (HER2-) tumors into intrinsic phenotypes with corresponding responses to neoadjuvant therapy (NAC). We performed reflex MP/BP assays on invasive breast cancer core biopsies and evaluated the relationships between clinical risk, molecular risk and intrinsic phenotype. Methods: 150 consecutive HR+, HER2- invasive breast cancers were identified by core biopsy in a tertiary care cancer center and underwent reflex MP/BP testing by an external central laboratory between July 2021 and Jan 2022. Retrospective review was completed on patient demographics and tumor characteristics; descriptive statistics were performed. Results: Of 150 newly diagnosed HR+ HER2- breast cancers, 141 successfully had a reflex MP/BP test performed; 9 were not performed due to technical feasibility or clerical error. Of the 141 patients with a completed MP/BP assay, 7 had recurrent disease, and 8 had metastatic disease, these were excluded. Patients were categorized as clinically high (cHR) or low risk (cLR) using the criteria from the MINDACT trial and as molecularly high risk (MP HR) or low risk (MP LR) per their MP results. We then grouped patients with discordant clinical and molecular risk. We then examined clinical features and NAC receipt amongst these clinical and molecular risk groups. Conclusions: There was discordance between clinical and molecular risk in 38% of our cohort, 20% were cLR/MP and 18% were cHR/MP LR. The decision to give NAC was primarily driven by clinical risk as only 1 patient with cLR/MP HR received NAC. Amongst cHR/MP LR 87% did not get NAC, but this appears to have been a clinical decision as only 7 of these patients had a pre-operative oncology visit at which MP/BP was mentioned. Most (72%) of &gt; cN1 patients received NAC, of the 5 who didn’t, 4 were in the MP LR group and had a pre-operative oncology visit where MP was mentioned. In this select group the genomic assay may have influenced the decision to withhold NAC. Reflex genomic assays for HR+ HER2- breast cancer may not be useful; the decision to integrate molecular risk into the decision for NAC is multifactorial and stage of disease may be most impactful. Further work is needed in this area. [Table: see text] [Table: see text]
The use of minimal residual disease in patients with high-risk breast cancer.
Authors: Alyssa Kameoka, Jami Aya Fukui
Journal: Journal of Clinical Oncology (2023)

e12521 Background: Breast cancer is the most frequently diagnosed cancer worldwide and the second leading cause of cancer death in women in the United States. Despite being disease-free after primary treatment, studies have shown that up to 30% of patients present with disease recurrence. Circulating tumor DNA (ctDNA) in blood is a minimally invasive technique to characterize individual cancer biology and monitor disease. Previous studies have demonstrated that ctDNA can be a sensitive and specific approach to breast cancer follow up and surveillance of disease recurrence for all subtypes. Methods: We evaluated 38 high risk breast cancer patients utilizing a personalized and tumor-informed ctDNA assay at 3-6 month intervals. We defined high risk as: any stage III disease, triple negative breast cancer (TNBC) or HR-/HER2+ breast cancer who received neoadjuvant chemotherapy treatment (NACT), pregnancy associated breast cancer, metastatic breast cancer without any evidence of disease, history of bilateral breast cancer, high risk genetics (i.e. BRCA1 or BRCA2 mutations), young age at diagnosis (&lt;40 years old) and/or breast cancer recurrence of any subtype. Results: Patient ages ranged from 34 to 83 (average: 53.3 years old) and included a diverse race/ethnicity population: White (n=12, 31%), Japanese (n=9, 23.7%), Native Hawaiian (n=6, 15.8%), Chinese (n=4, 10.5%), Filipino (n=4, 10.5%), Black (n=1, 2.6%), Hispanic (n=1, 2.6%), and Korean (n=1, 2.6%). Of the 38 cases, there was one ctDNA positive finding seen in a high risk case (young age at diagnosis and BRCA2 mutation) of clinical stage IIA HR+/HER2- breast cancer. After NACT, bilateral mastectomies, and radiation, patient remained on tamoxifen (declined ovarian function suppression) and was initially ctDNA negative until a second test identified detectable ctDNA. Restaging scans however did not show any evidence of disease. A third ctDNA test three months later, continued to be positive without any evidence of disease. All other cases showed negative ctDNA testing with an average of 1.55 ctDNA tests done per patient over two years. However, one case of clinical stage IIB TNBC had contralateral recurrence despite negative testing. After receiving NACT, bilateral mastectomies, post-operative paclitaxel and radiation, two ctDNA tests done three months apart were negative. Conclusions: There is potential use for this ctDNA platform in high risk breast cancer patients but larger studies need to be done. [Table: see text]
Beneficial effect of repeated participation in breast cancer screening upon survival.
Authors: Robert A. Smith, Stephen W Duffy, Amy Ming-Fang Yen, László Tabár, Abbie Ting-Yu Lin, Sam Li-Sheng Chen, Chen-Yang Hsu, Peter Dean, Tony Hsiu-Hsi Chen
Journal: Journal of Clinical Oncology (2023)

552 Background: The benefit of mammography screening in reducing population mortality from breast cancer is well established. However, the effect of repeated participation at scheduled screens on case survival is less well documented. Methods: In this retrospective analysis of breast cancer survival, we analyzed incidence and survival data on 37,079 women ages 40-69 from nine Swedish counties who had between one and five invitations to mammography screening and were diagnosed with breast cancer between 1992 and 2016. Of these, 4,564 subsequently died of breast cancer. For each breast cancer diagnosed in each county’s period of observation, we obtained data on previous screening history, and subsequent death (or not) from breast cancer. Formal comparisons of survival with respect to numbers of screening exams attended prior to a diagnosis of breast cancer were carried out using Cox proportional hazards regression with time-varying covariates, ie, cumulative numbers of screens, yielding hazard ratios and 95% confidence intervals (CI). We corrected for potential self-selection using the method of Duffy et al, which gives a corrected estimate based on the proportion of participants, the uncorrected estimate, and the relative risk of breast cancer death for non-participants compared to an uninvited population. Results: Depending on number of invitations, 58-73% (average 65%) participated in all scheduled screens, and 73-96% (average 91%) participated in at least one examination. There was successively better survival among women with increasing numbers of screening exams. For a woman with five previous screening invitations who participated in all five screening exams, the hazard ratio was 0.28 (95% CI 0.25-0.33, p&lt;0.0001), a 72% risk of dying from breast cancer, compared to a woman attending none. Following a conservative adjustment for potential self-selection factors, the hazard ratio was 0.34 (95% CI 0.26-0.43, p&lt;0.0001). Conclusions: For those women who develop breast cancer, regular prior participation in mammography screening confers significantly better survival. Most women will not develop breast cancer in their lifetime. These results indicate that for those who do, regular participation in screening considerably improves the probability of surviving it. The distinction between the general, population benefit of mammography screening, and the benefit of regular participation in mammography screening should be clearly articulated in breast cancer screening messaging and decision aids. [Table: see text]
A prospective, single-arm, single-center, exploratory clinical study of anlotinib combined with irinotecan in second-line and above treatment of HER-2–negative advanced breast cancer.
Authors: Ying Zhang, Wenhuan Xu, Yutian Zhao, Xuedan Guo, Tingting Hong, Yidan Yan, Xiaohong Wu
Journal: Journal of Clinical Oncology (2023)

e13114 Background: The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Irinotecan is a semi-synthetic water-soluble camptothecin derivative which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of irinotecan combined with anlotinib in second-line and above treatment of HER-2 negative advanced breast cancer. (ChiCTR2000037448) Methods: This open-label, single-arm, phase II study enrolled women aged 18 years and older with HER2-negative breast cancer who underwent ≥1 line chemotherapy, All patients were treated with irinotecan (60mg/m2, administered intravenously on Days 1 and 8 of each 21 day cycle) and anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle). The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety. Results: From November 2020 to November 2022, 14 patients were enrolled in this study. Median follow-up was 10.8 months (95% CI 4.3-17.3). Median PFS was 5.9 months (95% CI 2.0-9.8). Of all the patients whose efficacy could be evaluated (13/14), no patient achieved complete response (CR); 3(23.07%) and 8(61.54%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 23.1% (95% CI 5.0-53.8) and DCR was 84.6% (95% CI 54.6-98.1). OS has not reached. The major treatment-related adverse events (incidence≥10%) were fatigue (42.86%), hypertension (42.86%), neutropenia (28.57%), hand foot syndrome (21.43%) and myelosuppression (14.29%). There is no grade 3/4 adverse events occurred.28.57% (4/14) of patients had dose reductions. Conclusions: The combination of irinotecan and anlotinib showed better treatment response and tolerable toxicity in the treatment of second-line and above patients with HER2-negative metastatic breast cancer. Further studies enrolling more patients are still needed. Clinical trial information: ChiCTR2000037448 .
Lowering the bar for consideration of neoadjuvant chemotherapy in early-stage HER2-positive breast cancers.
Authors: Manasi Manoj Godbole, Matthew Meranda, Kathren Shango, Vrushali S. Dabak
Journal: Journal of Clinical Oncology (2023)

e12534 Background: The use of neoadjuvant chemotherapy (NAC) has contributed to increased rates of disease-free survival (DFS) as well as overall survival in breast cancer patients, specifically those with HER2-positive disease. Stage 2 patients with HER2-positive disease including tumors &gt; 2cm as well as node positive disease receive neoadjuvant chemotherapy as per current NCCN guidelines. The aim of our study was to understand outcomes in patients with early breast cancer receiving chemotherapy. Methods: We extracted data on patients with initial clinical stages IA-IB breast cancer who had HER2-positive status on initial biopsy and received chemotherapy plus anti-HER2 therapy in the Henry Ford Health System between January 2016 to June 2020. Patients with T2 or above and/or node positive disease were excluded. Results: Of the 229 total patients that met eligibility criteria, 159 (71%) were white, 65 (28%) were African American. 99% were females. The median age at diagnosis was 61 years. Estrogen receptor positivity was noted in 85% (196/229) of the patients. NAC was given to 56 patients (24%) of which 26 (46%) were African American and 45 (80%) were hormone receptor positive. 5 (9%) patients achieved pathological complete remission (CR). Remaining 51 patients (91%) did not have pathological CR. Of these, 17 (33%) patients had the same stage at surgery after NAC and 34 (66%) were upstaged on final pathological evaluation. 21 patients with residual disease (41%) underwent treatment change in the form of either ado-trastuzumab emtasine (TDM-1) or additional radiation therapy or repeat surgery. Of note, 34 of the 51 patients were treated for residual disease after 2019 with TDM-1. 54 (95%) patients are alive currently. Of the 173 patients that received adjuvant chemotherapy (76%), 39 (23%) were African American and 150 (87%) had hormone receptor positive disease. 19 of these (11%) were upstaged at surgery compared to the initial biopsy requiring treatment change. 163 (94%) are alive currently with no disease recurrence. Conclusions: Our study results suggest that NAC is used in minority of breast cancer patients, especially with stages 1A and 1B. Pathological CR rate in our study population was low and majority of patients who got NAC as well as a small percent of those who received adjuvant chemotherapy had disease upstaged based on surgical pathology results. We believe that this could be because of inaccurate initial staging due to limitations of imaging techniques and our population being mostly hormone receptor positive. With approval of TDM-1 in patients with residual disease post NAC, we may be able to improve outcomes in terms of recurrences and survival in these patients. Thus, consideration of NAC for early stage HER2-positive breast cancers appears attractive and data like our study may support ongoing prospective clinical trials.
ERBB2 mRNA expression to distinguish HER2-low/neg breast cancer prognosis.
Authors: Yueping Liu, Hong Lv, Mengjia Shen, Ruohong Shui, Feng Ye, Yue Meng, Ying Jia, Chao Liu, Shun An, Xiaoying Yuan, Xingmin Li, Wentao Yang, Hong Bu
Journal: Journal of Clinical Oncology (2023)

569 Background: Antibody-drug conjugates such as Trastuzumab deruxtecan significantly improved progression-free and overall survival for the HER2 low expression (HER2-low) breast cancer (BC) patients, pushing the research field of HER2-low to a new climax. In fact, the traditional immunohistochemistry (IHC) to identify the HER2-low or HER2-negative expression (HER2-neg) has been challenged, and it cannot predict the prognosis of HER2-low/neg patients well. Methods: Three pathologists evaluated the HER2 expression status of the subjects via IHC. More than two pathologists judged HER2 0-2 and FISH negative samples were included in this trial. ERBB2 mRNA level of formalin-fixed, paraffin-embedded BC post-surgery specimens were detected by MammaTyper quantitative real-time polymerase chain reaction (qRT-PCR) kit. The consistency of HER2 immunohistochemistry (IHC) and MammaTyper results were analyzed by interclass correlation coefficients (ICC). Differences in disease-free survival (DFS) were assessed by Kaplan Meier analysis. Results: 793 cases were included. The ICC value between IHC and MammaTyper, assessed for HER2-neg vs HER2-low is 0.28. With a median follow up of 2.5 years, there were 36 events in the whole subjects. In the whole subjects, MammaTyper successfully showed that the prognosis of HER2-low was significantly better than HER2-neg (P &lt; 0.001, HR = 3.497, 95%CI,1.807-6.77), but IHC could not distinguished them (P = 0.1071, HR = 1.776, 95%CI, 0.9194-3.43). Although the follow-up time is short, HER2-low subjects also showed better prognosis than HER2-neg in TNBC subjects distinguished by MammaTyper (P = 0.0271, HR = 2.912, 95%CI,1.129-7.511), not by IHC (P = 0.1032, HR = 2.213, 95%CI, 0.8512-5.756). However, in 291 cases of IHC and MammaTyper detection discordancy group, IHC results showed that the prognosis of HER2-low was worse, which was contrary to the MammaTyper results and the results of the above overall test results, suggesting that IHC could not verily reflect the amount of HER2 expression in some samples, and the prognosis of HER2-low population might be more related to the mRNA expression of HER2. Conclusions: Compared with IHC/FISH, MammaTyper qRT-PCR assay may actually reflect the prognosis of HER2-neg/low, which is expected to become a diagnostic beacon for HER2-low target drugs.
Longitudinal trends in serum calcium, parathormone and bone mineral density in breast cancer survivors on aromatase inhibitor therapy: A single institutional cohort study.
Authors: Sharmeen Sorathia, Olisaemeka Ogbue, Serhan Unlu, Abdel Rahman Nanah, Fatima Abdeljaleel, Sura Alqaisi, Dina Serhal, Abdo S. Haddad, Hamed Daw
Journal: Journal of Clinical Oncology (2023)

e12531 Background: Aromatase inhibitors (AIs), when used as adjuvant treatment of hormone receptor positive breast cancer, have been associated with bone density loss. However, any impact on PTH and by extension calcium (Ca) homeostasis is yet to be elucidated as no study till date has investigated longitudinal trends in parathyroid hormone (PTH) while on AI therapy. We explored these to determine if long term AI therapy was associated with hyperparathyroidism. Methods: This is a retrospective study of female breast cancer patients at the Cleveland Clinic Foundation started on AIs (anastrozole, letrozole and exemestane) from January 2015 to April 2022. Included patients had both baseline and subsequent data (after starting AI therapy), on serum Ca, PTH and lumbar spine T-scores (LsTs). These values were compared using paired t-test. Results: We identified n=9657 patients on AI therapy and included n=249 with pre and post AI PTH values. Among these, n= 209 received anastrozole, n=34 received letrozole and n=6 received exemestane. Cohort median age was 68 (IQR 62-72) years and median duration of AI therapy was 3 years. While we observed a significant positive correlation between change in Ca and change in PTH (p=0.02), the differences between baseline and treatment median serum Ca and PTH were not statistically significant. There was no significant association between changes in either serum Ca or PTH and change in LsTs (p-value: 0.69 and p-value: 0.05 respectively). Notably, 4% patients had elevated PTH and Ca after AI therapy was initiated among whom n=4 had markedly elevated PTH with low urinary Ca. Three of these four patients also had a diagnosis of chronic kidney disease (CKD) with normal vitamin D levels. Two patients with elevated PTH were on biotin supplements. There was an overall downtrend in LsTs (p-value: 0.0039) with no significant difference between the three AIs (p-value 0.0613). However, in comparison to other AIs, letrozole had the least depreciation in LsTs. Conclusions: Our findings do not suggest any correlation between AI therapy and hyperparathyroidism among breast cancer survivors. No significant increase in PTH levels occurred during AI therapy and majority of patients with clinically significant PTH elevation also had CKD, which may have contributed also to elevation of PTH level and low urinary calcium excretion.[Table: see text]
Antineoplastic and immunomodulating agent effects on immunization outcomes.
Authors: Jacob New, Jason Cham, Leah Puglisi, Lana Smith, Lee Hong, Russel Fielding, Sunil Kurian, Amitabh Pandey, Laura Nicholson
Journal: Journal of Clinical Oncology (2023)

1539 Background: Oncologists face a challenge in advising patients on the infection risk associated with antineoplastic and immunomodulating medications, as the extent of risk posed by each medication is not well understood. The rapid administration of COVID-19 immunizations across the population provides an opportunity to assess the influence of immunosuppressing medications on infection outcomes post-vaccination. This study evaluated the effect of antineoplastic and immunomodulating medications as classified by the World Health Organization Anatomical Therapeutic Chemical Classification System (WHO ATC) on post-vaccination risk of COVID-19 infection and antibody response to multiple SARS-CoV-2 epitopes using serial serologic assessments. Methods: At a large, tertiary healthcare system in San Diego, we conducted an observational cohort study from December 11, 2020, to September 22, 2022, comparing vaccinated adult patients taking WHO ATC-classified immunosuppressing medications (“immunosuppressed” group) with matched control patients not prescribed these medications (“immunocompetent” group) for the outcome of PCR+ COVID-19 infection. A subset of immunosuppressed and immunocompetent individuals was consented to provide serial assessments of antibody response to multiple SARS-CoV-2 epitopes using the Genalyte serologic platform. Results: 12,709 vaccinated immunosuppressed patients and 197,151 immunocompetent controls were identified for matched analysis. Receiving an immunosuppressing medication conferred increased risk of COVID-19 infection post-immunization (HR: 1.5, 95% CI: 1.38 – 1.63, p &lt; 0.0001). Among immunosuppressing medications, PD1/PD-L1 inhibiting monoclonal antibodies and calcineurin inhibitors were associated with increased risk of COVID-19 infection (HR: 2.33, 95% CI: 1.35 – 4.04, p = 0.0038; HR 2.72, 95% CI: 1.78 – 4.16, respectively). Receiving three and four COVID-19 immunizations reduced this risk, except in patients taking calcineurin inhibitors. Among 87 consented participants, 218 samples from multiple timepoints revealed a decreased antibody response to both spike S1 and S2 subunits following third and fourth immunization. Despite decreased seroconversion, this study found medications like CD20 inhibiting monoclonal antibodies and folic acid analogs did not increase the post-immunization risk of COVID-19. Conclusions: These results help elucidate the relationship between antineoplastic and immunomodulating medications and COVID-19 immunization outcomes. In our patients, seroconversion efficacy did not always correspond to post-immunization infection, consistent with COVID-19 disease risk being multifactorial. The findings of this study inform oncologists’ shared decision-making process in advising patients of the risk of infection associated with immunomodulating medications and the potential impact on their vaccination response.